Inhibition of pathological increased matrix metalloproteinase (MMP) activity for improvement of bone regeneration in diabetes
- Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db\(^{−}\)/db\(^{−}\)) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. \(\it Mmp3\), \(\it Mmp9\), \(\it Mmp13\) and gene expression of MMP inhibitor \(\it Timp2\) was significantly higher in regenerating bone fractures of db\(^{−}\)/db\(^{−}\) compared to wild type animals. \(\it Timp1\) and metalloproteinase \(\it AdamTS4\) showed no differences. In the second part, we locally applied a single dose (1 \(\mu\)L of 5 \(\mu\)M solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db\(^{−}\)/db\(^{−}\). We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db\(^{−}\)/db\(^{−}\) were restored significantly by application of Marimastat compared to PBS controls (\(\it n\) = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.
Author: | Johannes Maximilian WagnerORCiDGND, Felix ReinkemeierGND, Christoph WallnerGND, Mehran DadrasORCiDGND, Stephanie DittfeldGND, Marius DryschORCiDGND, Alexander Klaus SogorskiORCiDGND, Maxi von GlinskiORCiDGND, Marcus LehnhardtGND, Björn BehrORCiDGND, Mustafa BecerikliORCiDGND |
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URN: | urn:nbn:de:hbz:294-99217 |
DOI: | https://doi.org/10.3390/life12020134 |
Parent Title (English): | Life |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/05/25 |
Date of first Publication: | 2022/01/18 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | MMP; Open Access Fonds Marimastat; bone regeneration; diabetes; gene expression |
Volume: | 12 |
Issue: | 2, 134 |
First Page: | 134-1 |
Last Page: | 134-11 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Klinik für Plastische Chirurgie und Schwerbrandverletzte |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |